CN101133016A - Method for producing substituted biphenyls - Google Patents
Method for producing substituted biphenyls Download PDFInfo
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- CN101133016A CN101133016A CNA2006800067062A CN200680006706A CN101133016A CN 101133016 A CN101133016 A CN 101133016A CN A2006800067062 A CNA2006800067062 A CN A2006800067062A CN 200680006706 A CN200680006706 A CN 200680006706A CN 101133016 A CN101133016 A CN 101133016A
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- palladium
- phenyl
- boric acid
- chloro
- phosphine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/07—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms
- C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
- C07C205/12—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings the six-membered aromatic ring or a condensed ring system containing that ring being substituted by halogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/07—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms
- C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
Abstract
The invention relates to a method for producing substituted biphenyls (I) in which: R<1> = nitro, amino or NHR<3>: R<2> = CN, NO2, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6alkynyl, C1-C6-alkoxy, C1-C6 alkyl halide, C1-C6 alkylcarbonyl or phenyl; R3 = C1-C4alkyl, C2-C4 alkenyl or C2-C4 alkynyl; m = 1 or 2, and; n = 0 to 3. The invention is characterized in that a compound (II) is reacted with a diphenyl borinic acid (III) in the presence of a base and of a palladium catalyst selected from the group consisting of: a) palladium-trialkylphosphine or trialkylphosphine complex with palladium being zero in the oxidation state; b) salt of the palladium in the presence of triarylphosphine or trialkylphosphine serving as a complex ligand or; c) optionally, metallic palladium raised on substrates, in the presence of triarylphospine or trialkylphosphine in a solvent.
Description
The present invention relates to the method for the substituted biphenyl of a kind of preparation formula I:
Wherein substituting group is as giving a definition:
R
1Be nitro, amino or NHR
3,
R
2Be cyano group, nitro, halogen, C
1-C
6Alkyl, C
2-C
6Alkenyl, C
2-C
6Alkynyl, C
1-C
6Alkoxyl group, C
1-C
6Haloalkyl, (C
1-C
6Alkyl) carbonyl or phenyl,
R
3Be C
1-C
4Alkyl, C
2-C
4Alkenyl or C
2-C
4Alkynyl,
M is 1 or 2, wherein under the situation of m=2, and two R
1Group can have different definition,
N is 0,1,2 or 3, wherein under the situation of n=2 or 3, and two R
2Group can have different definition,
This method comprises that the phenylbenzene boric acid that makes formula II compound and formula (III) in the presence of alkali and palladium catalyst, reacts in solvent:
Wherein Hal is a halogen, R
1With m separately as defined above,
R wherein
2With n separately as defined above,
Wherein said palladium catalyst is selected from: a) wherein palladium is the palladium-triaryl phosphine title complex or the palladium-trialkyl phosphine title complex of zero oxidation state, b) the palladium salt under triaryl phosphine or trialkyl phosphine exist as ligand, or c) if the suitable palladium metal that puts on the carrier in the presence of triaryl phosphine or trialkyl phosphine
Wherein used triaryl phosphine or trialkyl phosphine can be substituted.
Tetrahedron Lett.32, the 2277th page (1991) have been introduced the phenyl-boron dihydroxide of use [1,4-two (diphenylphosphine) butane] palladium chloride (II) catalyzer and the linked reaction between the chlorobenzene and have only been carried out with 28% yield.
EP-A 0888261 discloses a kind of by make the method for chloronitrobenzene and phenyl-boron dihydroxide prepared in reaction nitrobiphenyl in the presence of palladium catalyst and alkali.In the method, need very high catalyst concn.
Therefore, the purpose of this invention is to provide a kind of can carrying out with industrially scalable, the economically viable method of regioselectivity ground preparation substituted biphenyl, this method is carried out under the palladium catalyst concentration that reduces.
Therefore, found the defined method of beginning.
Phenylbenzene boric acid (III) is by making optional phenyl-magnesium-chloride V that replaces and trialkylboron acid esters in the tetrahydrofuran (THF) as solvent, and 1 reaction obtains according to scheme, and wherein the trialkylboron acid esters is preferably trimethyl borate.
Scheme 1:
R
4Be C
1-C
4Alkyl, preferable methyl.
The vital used chlorobenzene (IV) that is based on of the high yield of phenylbenzene boric acid (III) is used only 0.7 normal trialkylboron acid esters.Use about 1.1 normal trialkylboron acid esters to produce as EP-A 0888261 described phenyl-boron dihydroxide.
With regard to the preparation of nitrobiphenyl (I), the reduction of trialkylboron acid esters consumption has several surprising advantages.Increased space-time yield.Because the reduction of expensive trimethyl borate consumption, and reduced the cost of raw material.Be different from the phenyl-boron dihydroxide that uses among the EP-A 0888261, this phenylbenzene boric acid (III) is dissolved in tetrahydrofuran (THF), and this causes the improvement of the heat extraction in the reaction process, and this is accompanied by the consumption of lower cooling power.This correspondingly makes the security of technology higher.
Temperature of reaction in this operation stage is 10-30 ℃, preferred 15-25 ℃.
Substituted biphenyl by present method preparation has following preferred substituents:
R
1Nitro, amino, methylamino, propyl group amino, butyl amino, allyl amino or propargyl amino,
More preferably nitro, amino or methylamino,
Most preferably nitro or amino;
R
2Cyano group, nitro, fluorine, chlorine, bromine, methyl, ethyl, propyl group, butyl, allyl group, propargyl, methoxyl group, oxyethyl group, trifluoromethyl or phenyl,
More preferably fluorine, chlorine, methyl or methoxy,
Fluorine or chlorine most preferably;
R
3Methyl, ethyl, propyl group, butyl, allyl group or propargyl,
More preferably methyl, ethyl or propargyl,
Most preferable;
m1；
N0,1 or 2, preferred 0 or 1, most preferably 1.
Carry out subsequently homogeneous catalysis Suzuki diaryl cross-coupling according to scheme 2.Scheme 2:
1. aqueous NaOH
2.Pd precursor/part
Preferably from R wherein
2With n separately as defined above the phenylbenzene boric acid of formula (III) begin.
In addition, preferred raw material is that wherein n is 0 or 1, particularly 1 phenylbenzene boric acid.
Two (4-aminomethyl phenyl) boric acid very particularly preferably, two (4-fluoro phenyl) boric acid, particularly two (4-chloro-phenyl-) boric acid is as initial compounds (III).
Preferably from having single nitro or amino compound (II) (m=1), especially 4-nitro-chlorobenzene or 4-amino-chloro-benzene, particularly 2-nitro-chlorobenzene or 2-amino-chloro-benzene.
Compound (II) uses with equimolar amount usually based on phenylbenzene boric acid (III) (phenylbenzene boric acid Equivalent), and preferably with 20% excessive at the most, preferred 50% excessive amount is at the most used.
Used alkali can be organic bases, for example tertiary amine.Preference is as using triethylamine or dimethylcyclohexylamine.
Used alkali is form of mixtures preferably, especially independent alkali metal hydroxide, alkaline earth metal hydroxides, alkaline carbonate, alkaline earth metal carbonate, alkali metal hydrocarbonate, alkali metal acetate, alkaline-earth metal acetate, alkali metal alcoholates and alkaline-earth alkoxides.
Particularly preferred alkali is alkali metal hydroxide, alkaline earth metal hydroxides, alkaline carbonate, alkaline earth metal carbonate and alkali metal hydrocarbonate.
Especially preferred alkali is alkali metal hydroxide, for example, and sodium hydroxide and potassium hydroxide and alkaline carbonate and alkali metal hydrocarbonate, for example, Quilonum Retard, yellow soda ash and salt of wormwood.
In the method for the invention, preferably with 100-500mol%, more preferably use by the ratio of 150-400mol% in phenylbenzene boric acid (III) for base.
The palladium catalyst that is fit to is that wherein palladium is the palladium-ligand-complexes of zero oxidation state, and if the palladium salt in the presence of ligand is the perhaps preferred suitable palladium metal that puts on the carrier in the presence of ligand.
The ligand that is fit to is not charged part, as choosing substituted triaryl phosphine and trialkyl phosphine on aryl rings wantonly, and as triphenylphosphine (TPP), two-1-adamantyl normal-butyl phosphine, tri-butyl phosphine (TtBP) or 2-(dicyclohexyl phosphino-) biphenyl.
And what document had also been described other structure class has reactive ligand especially, comprises 1,3-two (2, the 6-diisopropyl phenyl)-4,5-H2-imidazolitm chloride (referring to, for example, people such as G.A.Grasa, Organometallics 2002,21,2866) and tricresyl phosphite (2, the 4-di-tert-butyl-phenyl) ester (referring to people such as A.Zapf, Chem.Eur.J.2000,6,1830).
By adding quaternary ammonium salt, as tetra-n-butyl ammonium bromide (TBAB) can increase ligand reactivity (referring to, for example, people such as D.Zim, Tetrahedron Lett.2000,41,8199).
If necessary, the water-soluble of palladium complex can be improved by the substituting group such as sulfonic acid or sulfonate groups, carboxylic acid or carboxylate groups, phosphonic acids, or phosphonate groups, all alkyl ammonium, hydroxyl and polyether group.
At palladium is in the palladium-ligand-complexes of zero oxidation state, preferably uses tetrakis triphenylphosphine palladium, also has four [three (o-tolyl) phosphine] palladium.
In the palladium salt that uses in the presence of ligand, palladium presents positive titanium dioxide attitude usually.Preferred Palladous chloride, palladium or the di acetonitrile palladium chloride of using.Especially preferably use Palladous chloride.
Usually, 6-60 equivalent, preferred 15-25 normal above-mentioned ligand, particularly triphenylphosphine and tri-butyl phosphine and 1 normal palladium salt binding.
EP-A 0888261 has described whenever the amount palladium catalyst uses the normal triphenylphosphine of 2-6.Think prevailingly in the document that it is disadvantageous using high excessive part because expect this will cause the catalytic activity title complex inactivation (referring to, for example, people such as J.Hassan, Chem.Rev.2002,102,1359).
Thereby it is shocking that high excessive ligand causes the total recovery in the inventive method to improve with combining of low consumption catalyzer, and has therefore improved economic feasibility.
Palladium metal is preferably used with form of powder or on solid support material, and for example palladium loads on the gac, and palladium loads on the aluminum oxide, palladium loads on the barium carbonate, and palladium loads on the barium sulfate, and palladium loads on the lime carbonate, palladium loads on all if you would holder on the native silico-aluminate, and palladium loads on SiO
2On, and palladium loads on the lime carbonate, the content of palladium is 0.5-12 weight % in each case.Except palladium and solid support material, these catalyzer can comprise other doping agents, and are for example plumbous.
When using suitable words to put on palladium metal on the carrier, especially preferably also use above-mentioned ligand, especially use at triphenylphosphine as the palladium on the gac of loading in the presence of the ligand, wherein the phenyl in the triphenylphosphine is preferably replaced by 1-3 sulfonate groups altogether.
In the methods of the invention, palladium catalyst uses with the low ratio of 0.001-1.0 mole % based on compound (II), preferred 0.005-0.5 mole % or 0.01-0.5 mole %, especially 0.005-0.05 mole %.
The low amount of making of palladium salt has constituted the significant cost advantage of present method for art methods with combining of the high consumption of ligand.
The inventive method can promptly be carried out in the biphasic system that catalyzer is formed by water and solid phase.In this case, water also comprises water-miscible organic solvent outside can dewater.
The organic solvent that is applicable to the inventive method is an ether, as glycol dimethyl ether, diglyme, tetrahydrofuran (THF), two alkane and t-butyl methyl ether, hydrocarbon, as normal hexane, normal heptane, hexanaphthene, benzene, toluene and dimethylbenzene, alcohol, as methyl alcohol, ethanol, 1-propyl alcohol, 2-propyl alcohol, ethylene glycol, 1-butanols, 2-butanols and the trimethyl carbinol, ketone, as acetone, ethyl methyl ketone and isobutyl methyl ketone, acid amides, as dimethyl formamide, N,N-DIMETHYLACETAMIDE and N-Methyl pyrrolidone, every kind of situation is used separately or the mixing use.
Preferred solvent is an ether, for example glycol dimethyl ether, tetrahydrofuran (THF) and two alkane, and hydrocarbon, as hexanaphthene, toluene and dimethylbenzene, alcohol, as ethanol, 1-propyl alcohol, 2-propyl alcohol, 1-butanols and the trimethyl carbinol, every kind of situation is used separately or is mixed and use.
In the particularly preferred scheme of the inventive method, make water, one or multiple water-insoluble and one or multiple water-soluble solvent, the for example mixture of water and two alkane, the perhaps mixture of water and tetrahydrofuran (THF), perhaps water, two alkane and alcoholic acid mixture, or water, tetrahydrofuran (THF) and methanol mixture, the perhaps mixture of water, toluene and tetrahydrofuran (THF), the mixture of preferably water and tetrahydrofuran (THF), perhaps water, tetrahydrofuran (THF) and methanol mixture.
Usually, based on every mole compound (II), the solvent total amount is 3000-500g, preferred 2000-700g.
Suitably, present method is following carries out: the palladium catalyst of compound (II), phenylbenzene boric acid (III), alkali and catalytic amount is added in the mixture of water and one or more inert organic solvents, at 50 ℃-120 ℃, preferred 70 ℃-110 ℃, more preferably stirred 1-50 hour preferred 2-24 hour under 90 ℃-100 ℃ the temperature.
Depend on employed solvent and temperature, set up the 1-6 crust, the pressure of preferred 1-4 crust.
Preferred this is reflected in water and the tetrahydrofuran (THF) and carries out.
This reaction can be carried out in the conventional equipment that is fit to this method.
When reaction is finished, for example, remove the solvent in the crude product by removing by filter the palladium catalyst that obtains with solid.
At product is under the non-complete water miscible situation, removes water-soluble palladium catalyzer or ligand when aqueous phase separation from crude product fully.
Subsequently, further purifying is can be by the person skilled in the art known and be applicable to that the method for concrete product realizes, for example by recrystallization, distillation, distillation, zone melting, melt crystallization or chromatography realize.
By method of the present invention, for example can be prepared as follows compound:
4 '-chloro-2 nitro biphenyl,
4 '-chloro-2-phenylaniline,
4 '-fluoro-2 nitro biphenyl,
4 '-fluoro-2-phenylaniline,
4 '-methyl-2 nitro biphenyl,
4 '-methyl-2-phenylaniline,
4 '-methoxyl group-2 nitro biphenyl,
4 '-methoxyl group-2-phenylaniline,
4 '-bromo-2 nitro biphenyl,
4 '-bromo-2-phenylaniline,
3 '-fluoro-2 nitro biphenyl,
3 '-fluoro-2-phenylaniline,
3 '-chloro-2 nitro biphenyl,
3 '-chloro-2-phenylaniline,
3 '-bromo-2 nitro biphenyl,
3 '-bromo-2-phenylaniline,
3 '-methyl-2 nitro biphenyl,
3 '-methyl-2-phenylaniline,
3 '-methoxyl group-2 nitro biphenyl,
3 '-methoxyl group-2-phenylaniline,
4 '-phenyl-2 nitro biphenyl,
4 '-phenyl-2-phenylaniline,
4 '-trifluoromethyl-2 nitro biphenyl,
4 '-trifluoromethyl-2-phenylaniline,
4 '-fluoro-4-nitrobiphenyl,
4 '-fluoro-4-phenylaniline,
4 '-chloro-4-nitrobiphenyl,
4 '-chloro-4-phenylaniline,
4 '-bromo-4-nitrobiphenyl,
4 '-bromo-4-phenylaniline,
4 '-methyl-4-nitrobiphenyl,
4 '-methyl-4-phenylaniline,
4 '-cyano group-4-nitrobiphenyl,
4 '-cyano group-4-phenylaniline,
2 nitro biphenyl,
The 2-phenylaniline,
The 4-nitrobiphenyl,
The 4-phenylaniline.
The inventive method is with extraordinary purity, providing Compound I up to quantitative very high yield.
Can be suitable as the precursor of substituted biphenyl amine by the biphenyl that the inventive method obtains, the latter be again farm crop fungicidal protection activity composition intermediate (referring to, for example, EP-A 545099).
Synthesizing of 4 '-chloro-2 nitro biphenyl
1: two (4-chloro-phenyl-) boric acid of embodiment
The solution of 120g trimethyl borate and 590g tetrahydrofuran (THF) is cooled to 11 ℃.In 2 hours, be metered into the tetrahydrofuran solution of the 4-chloro-phenyl-magnesium chloride of 1000g 20 weight % to this solution.In this process, set up 20-21 ℃ temperature.After all adding, under 20 ℃ with reaction soln restir 1 hour.
Stirred 30 minutes down with the aqueous hydrochloric acid reaction mixture of 621g 10% and at 40 ℃ subsequently.After being separated, obtain the tetrahydrofuran solution (transformation efficiency 87%) of 1500g two (4-chloro-phenyl-) boric acid.Organic phase can be used as crude product and further processes, and perhaps can separate two (4-chloro-phenyl-) boric acid with column chromatography on silica gel by the mixture that uses ethyl acetate and hexanaphthene.
The reaction of 2: two (4-chloro-phenyl-) boric acid of embodiment and 1-chloro-2-oil of mirbane
Under 15-20 ℃, the aqueous sodium hydroxide solution of the 240g 20 weight % that in autoclave, pack into earlier.In 26 minutes, under 18-22 ℃, in this solution, be metered into the two alkane solution of two (4-chloro-phenyl-) boric acid of 539g 9-10 weight %.After all adding, reaction soln was stirred 40 minutes down at 18-22 ℃.Two alkane solution of the triphenylphosphine of 2.4g 50 weight % are joined in the reaction soln.After all adding, with reaction soln 18-22 ℃ of following restir 30 minutes.At last, (diacetonitrile) Palladous chloride (II) of 117mg and the 1-chloro-2-oil of mirbane of 84g are joined in the reaction soln.Reaction soln is heated to 100 ℃, continues 11.5 hours.In this process, set up the high pressure of 3.7 crust.
After two (4-chloro-phenyl-1) boric acid total overall reaction, reaction soln is cooled to 40-45 ℃, and with the pressurized vessel standard pressure that reduces pressure.Aqueous hydrochloric acid extractive reaction solution with 250g 10 weight %.After being separated, obtain two alkane solution (transformation efficiency 99%) of 4-chloro-2 '-nitrobiphenyl.Remove two alkane by distillation under reduced pressure, and can isolate 4-chloro-2 '-nitrobiphenyl by melt crystallization.
The reaction of 3: two (4-chloro-phenyl-) boric acid of embodiment and 1-chloro-2-oil of mirbane
Under 15-20 ℃, the aqueous sodium hydroxide solution of the 495g 20 weight % that in autoclave, pack into earlier.Under 18-22 ℃, be metered into the tetrahydrofuran solution of two (4-chloro-phenyl-) boric acid of 1000g 11 weight % in 30 minutes in introversive this solution.After all adding, reaction soln was stirred 30 minutes down at 18-22 ℃.The tetrahydrofuran solution of the triphenylphosphine of 3.5g 50 weight % is added in the reaction soln.After all adding, reaction soln was stirred 30 minutes down at 20-21 ℃.At last, in reaction soln, be added on 0.9g Palladous chloride (II) in the 227g fused 1-chloro-2-oil of mirbane.Reaction soln is heated to 100 ℃, continues 6-8 hour.In this process, in autoclave, set up the high pressure of 3.0 crust.
After two (4-chloro-phenyl-) boric acid complete reaction, with reduce pressure standard pressure and reaction soln is cooled to 40-50 ℃ of autoclave.Aqueous hydrochloric acid extractive reaction solution with 450g 10 weight %.After being separated, obtain the tetrahydrofuran solution (transformation efficiency 99%) of 4-chloro-2 '-nitrobiphenyl.
The reaction of 4: two (4-chloro-phenyl-) boric acid of embodiment and 1-chloro-2-oil of mirbane
Under 20 ℃, the aqueous sodium hydroxide solution of the 770g 22 weight % that in 4L four neck flasks, pack into earlier.Under 20 ℃, be metered into the tetrahydrofuran solution of two (4-chloro-phenyl-) boric acid of 2045g 13 weight % in 30 minutes in introversive this solution.After all adding, reaction soln was stirred 30 minutes down at 20 ℃.With the 9.8g triphenylphosphine, 1.7g Palladous chloride (II) and 273g fused 1-chloro-2-oil of mirbane join in the reaction soln.Reaction soln is heated to reflux temperature, continues 20 hours.
After 4-chlorophenylboronic acid complete reaction, reaction soln is cooled to 40 ℃, the aqueous hydrochloric acid with 255g 35 weight % extracts subsequently.After being separated, obtain the tetrahydrofuran solution (transformation efficiency 99%) of 4-chloro-2 '-nitrobiphenyl.
The reaction of embodiment 5:4-chlorophenylboronic acid and 1-chloro-2-oil of mirbane
Under 18-22 ℃, earlier to 4m
3Reactor in pack into the tetrahydrofuran solution of 4-chlorophenylboronic acid of 1773kg 13 weight %.In 20 minutes 22-30 ℃ and stir under be metered into aqueous sodium hydroxide solution and the 140kg water of 538kg 25 weight %.After all adding, reaction soln was stirred 30 minutes down at 22-25 ℃.With the 2.28kg triphenylphosphine, 372g Palladous chloride (II) and 252kg fused 1-chloro-2-oil of mirbane join in the reaction soln.Reaction soln is heated to 66 ℃, continues 18 hours.After 4-chlorophenylboronic acid complete reaction, reaction soln is cooled to 45 ℃, with the aqueous hydrochloric acid extraction of 794kg 10 weight %.After being separated, obtain the tetrahydrofuran solution (transformation efficiency 99%) of 4-chloro-2 '-nitrobiphenyl.
The reaction of 6: two (4-chloro-phenyl-) boric acid of embodiment and 1-chloro-2-oil of mirbane
Under 15 ℃, the aqueous sodium hydroxide solution of the 117g 20 weight % that in autoclave, pack into earlier.Under 18-22 ℃, be metered into the tetrahydrofuran solution of two (4-chloro-phenyl-) boric acid of 415g 9-10 weight % in 30 minutes in introversive this solution.After all adding, reaction soln was stirred 30 minutes down at 18-22 ℃.The tetrahydrofuran solution of the tri-butyl phosphine of 0.24g 50 weight % is joined in the reaction soln.After all adding, reaction soln was stirred 30 minutes down at 18-20 ℃.At last, with the Palladous chloride (II) of 104g 10 weight % in 10 weight % aqueous hydrochloric acids solution and the tetrahydrofuran solution of the 1-chloro-2-oil of mirbane of 91g 85 weight % add in the reaction soln.Reaction soln is heated to 100 ℃, continues 12 hours.In this process, set up the high pressure of 3.5 crust.
After two (4-chloro-phenyl-) boric acid complete reaction, reaction soln is cooled to 40-50 ℃, and pressurized vessel is decompressed to standard pressure.Aqueous hydrochloric acid extractive reaction solution with 125g 10 weight %.After being separated, obtain the tetrahydrofuran solution (transformation efficiency 85%) of 4-chloro-2 '-nitrobiphenyl.
The reaction of 7: two (4-chloro-phenyl-) boric acid of embodiment and 1-bromo-2-aniline
Under 20 ℃, the aqueous sodium hydroxide solution of the 240g 20 weight % that in autoclave, pack into earlier.Under 20 ℃, be metered into the tetrahydrofuran solution of two (4-chloro-phenyl-) boric acid of 539g 9-10 weight % in 30 minutes in introversive this solution.After all adding, reaction soln was stirred 30 minutes down at 20 ℃.The tetrahydrofuran solution of the triphenylphosphine of 1.3g 50 weight % is joined in the reaction soln.After all adding, reaction soln was stirred 30 minutes down at 20 ℃.At last, with the Palladous chloride (II) of 320mg 10 weight % in 10 weight % hydrochloric acid solution and the tetrahydrofuran solution of the 1-bromo-2-aniline of 108g 85 weight % add in the reaction soln.Reaction soln is heated to 100 ℃, continues 12 hours.In this process, set up the high pressure of 3.5 crust.
After two (4-chloro-phenyl-) boric acid complete reaction, reaction soln is cooled to 40-50 ℃, and pressurized vessel is decompressed to standard pressure.After being separated, with the aqueous sodium hydroxide solution extracted organic phase of 100g 20 weight %.Obtain the tetrahydrofuran solution (transformation efficiency 85%) of 4-chloro-2 '-nitrobiphenyl.Remove tetrahydrofuran (THF) by distillation under reduced pressure, go out 4-chloro-2 '-nitrobiphenyl by Crystallization Separation.
Claims (15)
1. the method for the substituted biphenyl of a preparation formula I:
Wherein substituting group is as giving a definition:
R
1Be nitro, amino or NHR
3,
R
2Be cyano group, nitro, halogen, C
1-C
6Alkyl, C
2-C
6Alkenyl, C
2-C
6Alkynyl, C
1-C
6Alkoxyl group, C
1-C
6Haloalkyl, (C
1-C
6Alkyl) carbonyl or phenyl,
R
3Be C
1-C
4Alkyl, C
2-C
4Alkenyl or C
2-C
4Alkynyl,
M is 1 or 2, wherein under the situation of m=2, and two R
1Group can have different definition,
N is 0,1,2 or 3, wherein under the situation of n=2 or 3, and two R
2Group can have different definition,
This method comprises makes formula II compound and phenylbenzene boric acid (III) in the presence of alkali and palladium catalyst, reacts in solvent:
Wherein Hal is a halogen, R
1With m separately as defined above,
R wherein
2With n separately as defined above,
Wherein said palladium catalyst is selected from: a) wherein palladium is the palladium-triaryl phosphine title complex or the palladium-trialkyl phosphine title complex of zero oxidation state, b) the palladium salt under triaryl phosphine or trialkyl phosphine exist as ligand, or c) if the suitable palladium metal that puts on the carrier in the presence of triaryl phosphine or trialkyl phosphine
Wherein used triaryl phosphine or trialkyl phosphine can be substituted.
2. according to the process of claim 1 wherein that the compound (II) that uses is the 2-nitro-chlorobenzene.
3. according to the method for claim 1 or 2, wherein initial compounds (III) is the substituted phenylbenzene boric acid in the 4-position only.
4. according to the method for claim 1 or 2, wherein use to have fluorine, chlorine or methyl as the unique substituent phenylbenzene boric acid (III) on the 4-position.
5. according to the method for claim 1 or 2, wherein initial compounds (III) is two (4-chloro-phenyl-) boric acid.
6. according to each method among the claim 1-5, use therein palladium catalyst according to claim 1 is tetrakis triphenylphosphine palladium or four (tri-butyl phosphine) palladium a).
7. according to each method among the claim 1-5, wherein use palladium catalyst b) according to claim 1.
8. according to each method among the claim 1-5, use therein palladium catalyst c according to claim 1) be by the palladium metal on the gac of loading in the presence of the triphenylphosphine of 1-3 sulfonate groups replacement altogether at its phenyl.
9. according to the method for claim 7, the salt b of use therein palladium catalyst) be Palladous chloride, palladium or two acetonitrile Palladous chloride.
10. according to the method for claim 7, palladium catalyst b wherein) with based on whenever amount palladium salt uses the mode of the normal triphenylphosphine of 6-60 to use.
11. according to the process of claim 1 wherein the palladium catalyst that uses 0.001-1.0 mole % based on compound (II).
12. carry out under the temperature that is reflected at 50-120 ℃ according to the process of claim 1 wherein.
13. carry out in the mixture that is reflected at water and organic solvent according to the process of claim 1 wherein.
14. according to the method for claim 13, wherein used organic solvent is an ether.
15. carry out under the pressure that is reflected at 1-6 crust according to the process of claim 1 wherein.
Applications Claiming Priority (3)
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| DE102005010107 | 2005-03-02 | ||
| PCT/EP2006/060400 WO2006092429A1 (en) | 2005-03-02 | 2006-03-02 | Method for producing substituted biphenyls |
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| CN101133016A true CN101133016A (en) | 2008-02-27 |
| CN101133016B CN101133016B (en) | 2010-06-02 |
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| CN2006800067062A Expired - Fee Related CN101133016B (en) | 2005-03-02 | 2006-03-02 | Method for producing substituted biphenyls |
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| EP (1) | EP1856024B2 (en) |
| JP (1) | JP5138386B2 (en) |
| KR (1) | KR20070113268A (en) |
| CN (1) | CN101133016B (en) |
| AR (1) | AR052930A1 (en) |
| AT (1) | ATE403639T1 (en) |
| AU (1) | AU2006219874A1 (en) |
| BR (1) | BRPI0607424B1 (en) |
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| DE (1) | DE502006001281D1 (en) |
| DK (1) | DK1856024T4 (en) |
| EA (1) | EA200701814A1 (en) |
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| IL (1) | IL184973A0 (en) |
| MX (1) | MX2007009457A (en) |
| PL (1) | PL1856024T3 (en) |
| SI (1) | SI1856024T1 (en) |
| UA (1) | UA87561C2 (en) |
| WO (1) | WO2006092429A1 (en) |
| ZA (1) | ZA200708352B (en) |
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| CN104529794A (en) * | 2014-12-26 | 2015-04-22 | 京博农化科技股份有限公司 | Method for preparing boscalid intermediate 2-(4-chlorophenyl) aniline |
| TWI488831B (en) * | 2008-05-09 | 2015-06-21 | Bayer Cropscience Ag | Process for preparing substituted biphenylanilides |
| CN105218378A (en) * | 2008-06-25 | 2016-01-06 | 巴斯夫欧洲公司 | Prepare the method for substituted biphenyl |
| CN105392791A (en) * | 2013-07-23 | 2016-03-09 | 拜耳作物科学股份公司 | Improved process for preparing chlorinated biphenylanilides and biphenylanilines |
| CN107266306A (en) * | 2009-07-07 | 2017-10-20 | 拜耳知识产权有限责任公司 | Prepare（The base of 2,4 dimethyl diphenyl 3）The method of acetic acid, its ester and midbody compound |
| CN109912425A (en) * | 2018-12-29 | 2019-06-21 | 京博农化科技有限公司 | A kind of preparation method of the chloro- 2 nitro biphenyl of 4`- |
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| WO2007138089A1 (en) | 2006-06-01 | 2007-12-06 | Basf Se | Process for preparing substituted biphenyls |
| EP2008991A1 (en) | 2007-06-29 | 2008-12-31 | Bayer CropScience AG | Method for manufacturing biaryls |
| US7821647B2 (en) * | 2008-02-21 | 2010-10-26 | Corning Incorporated | Apparatus and method for measuring surface topography of an object |
| EP2093216A1 (en) * | 2008-02-25 | 2009-08-26 | Bayer CropScience AG | Process for preparing substituted biphenylanilides |
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| JP5935123B2 (en) * | 2011-08-22 | 2016-06-15 | 国立研究開発法人産業技術総合研究所 | High temperature high pressure cross coupling method |
| CN104478725A (en) * | 2014-11-25 | 2015-04-01 | 天津市均凯化工科技有限公司 | Method for preparing 4'-chloro-2-nitro biphenyl |
| CN104478726A (en) * | 2014-12-01 | 2015-04-01 | 南通嘉禾化工有限公司 | Method of preparing 2-nitrobiphenyl compound |
| CN104529786B (en) * | 2014-12-16 | 2019-10-11 | 上海生农生化制品股份有限公司 | The synthetic method of the fluoro- 2 '-nitrobiphenyl of 3,4,5- tri- |
| JP7064216B2 (en) * | 2019-02-27 | 2022-05-10 | 国立大学法人 東京大学 | Alkoxyvinylidene compound production method, pyrazole compound production method |
| EP4341239A1 (en) * | 2021-05-19 | 2024-03-27 | Basf Se | Process for preparing substituted biphenyls via suzuki coupling of aryl-chlorides |
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| IL103614A (en) | 1991-11-22 | 1998-09-24 | Basf Ag | Carboxamides for controlling botrytis and certain novel such compounds |
| EA001071B1 (en) | 1996-03-13 | 2000-10-30 | Басф Акциенгезельшафт | Process for preparing nitrobiphenylene |
| US6362380B1 (en) * | 1996-03-13 | 2002-03-26 | Basf Aktiengesellschaft | Preparation of nitrobiphenyls |
| JP4203192B2 (en) * | 1998-10-26 | 2008-12-24 | 北興化学工業株式会社 | Process for producing nitrophenylphenol compounds |
| IL152159A0 (en) * | 2000-05-19 | 2003-05-29 | Lilly Co Eli | A process for preparing biphenyl compounds |
| DE10140857A1 (en) † | 2001-08-21 | 2003-03-06 | Clariant Gmbh | Process for the preparation of aryl and alkyl boron compounds in microreactors |
| JP4165858B2 (en) † | 2001-10-15 | 2008-10-15 | 北興化学工業株式会社 | tert-Amyloxyhalogenobenzene compound and method for producing the same, tert-amyloxycyanobiphenyl compound and method for producing the same, and method for producing cyanohydroxybiphenyl compound |
| EP1957439A2 (en) * | 2005-11-15 | 2008-08-20 | Syngeta Participations AG | Process for the production of biphenyls |
| WO2007138089A1 (en) * | 2006-06-01 | 2007-12-06 | Basf Se | Process for preparing substituted biphenyls |
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2006
- 2006-03-01 AR ARP060100769A patent/AR052930A1/en unknown
- 2006-03-02 WO PCT/EP2006/060400 patent/WO2006092429A1/en active IP Right Grant
- 2006-03-02 DK DK06708604.1T patent/DK1856024T4/en active
- 2006-03-02 EA EA200701814A patent/EA200701814A1/en unknown
- 2006-03-02 UA UAA200710866A patent/UA87561C2/en unknown
- 2006-03-02 ES ES06708604T patent/ES2308727T5/en active Active
- 2006-03-02 JP JP2007557512A patent/JP5138386B2/en not_active Expired - Fee Related
- 2006-03-02 KR KR1020077022402A patent/KR20070113268A/en not_active Application Discontinuation
- 2006-03-02 CA CA002598769A patent/CA2598769A1/en not_active Abandoned
- 2006-03-02 DE DE502006001281T patent/DE502006001281D1/en active Active
- 2006-03-02 EP EP06708604A patent/EP1856024B2/en not_active Not-in-force
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- 2006-03-02 AT AT06708604T patent/ATE403639T1/en active
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI488831B (en) * | 2008-05-09 | 2015-06-21 | Bayer Cropscience Ag | Process for preparing substituted biphenylanilides |
| CN105218378A (en) * | 2008-06-25 | 2016-01-06 | 巴斯夫欧洲公司 | Prepare the method for substituted biphenyl |
| CN107266306A (en) * | 2009-07-07 | 2017-10-20 | 拜耳知识产权有限责任公司 | Prepare（The base of 2,4 dimethyl diphenyl 3）The method of acetic acid, its ester and midbody compound |
| CN105392791A (en) * | 2013-07-23 | 2016-03-09 | 拜耳作物科学股份公司 | Improved process for preparing chlorinated biphenylanilides and biphenylanilines |
| CN105392791B (en) * | 2013-07-23 | 2019-02-22 | 拜耳作物科学股份公司 | The improved method for preparing chloro acyl benzidine and benzidine |
| CN104529794A (en) * | 2014-12-26 | 2015-04-22 | 京博农化科技股份有限公司 | Method for preparing boscalid intermediate 2-(4-chlorophenyl) aniline |
| CN109912425A (en) * | 2018-12-29 | 2019-06-21 | 京博农化科技有限公司 | A kind of preparation method of the chloro- 2 nitro biphenyl of 4`- |
Also Published As
| Publication number | Publication date |
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| JP2008531657A (en) | 2008-08-14 |
| BRPI0607424A2 (en) | 2010-04-06 |
| JP5138386B2 (en) | 2013-02-06 |
| ATE403639T1 (en) | 2008-08-15 |
| ES2308727T3 (en) | 2008-12-01 |
| US20080183021A1 (en) | 2008-07-31 |
| WO2006092429A1 (en) | 2006-09-08 |
| ZA200708352B (en) | 2009-07-29 |
| CN101133016B (en) | 2010-06-02 |
| IL184973A0 (en) | 2007-12-03 |
| SI1856024T1 (en) | 2008-12-31 |
| PL1856024T3 (en) | 2009-01-30 |
| AR052930A1 (en) | 2007-04-11 |
| CA2598769A1 (en) | 2006-09-08 |
| DK1856024T4 (en) | 2011-11-21 |
| AU2006219874A1 (en) | 2006-09-08 |
| EA200701814A1 (en) | 2008-02-28 |
| ES2308727T5 (en) | 2012-01-05 |
| MX2007009457A (en) | 2007-10-02 |
| EP1856024B2 (en) | 2011-08-17 |
| BRPI0607424B1 (en) | 2015-09-29 |
| UA87561C2 (en) | 2009-07-27 |
| DK1856024T3 (en) | 2008-11-24 |
| KR20070113268A (en) | 2007-11-28 |
| US7772446B2 (en) | 2010-08-10 |
| EP1856024A1 (en) | 2007-11-21 |
| DE502006001281D1 (en) | 2008-09-18 |
| EP1856024B1 (en) | 2008-08-06 |
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